Clint Allred

BRIEF BIO

Dr. Allred is an expert in the area of understanding the role that diet and endogenous and exogenous sources of hormonal activity play in the development and progression of epithelial derived cancers.  He has published many manuscripts (Cancer Research, Journal of Nutrition, the American Journal of Physiology-Gastrointestinal and Liver Physiology, and the Proceedings of the National Academy of Sciences) in this area which have significantly impacted the understanding of the physiological role of dietary components.  Many of these studies were conducted in vivoutilizing models of colonic tumorigenesis and inflammation.  The primary focus of Dr. Allred’s laboratory in the past twelve years has been to elicit the response of non-transformed colonocytes to endogenous hormones and xenoestrogens commonly found in the diet. His research uses molecular biology and preclinical modeling approaches to ascertain how the diet influences intestinal physiology.  Recently, he has begun to investigate the microbiome and the important role it plays in intestinal health.  Dr. Allred has extensively investigated how dietary components may act as ligands of nuclear receptors in non-malignant and fully transformed cancer cells.

CURRENT PROJECTS

• Diet induced modifications of microbiota metabolites in colon tumorigenesis.
• Arylhydrocarbon receptor mediated modulation of colorectal cancer by microbiota metabolites.
• To determine the role of endogenous and xenoestrogens and their metabolites in colonic inflammation.
• Effects of Estrogens on Sporadic and Inflammation-associated Colon Cancer.

SELECTED PUBLICATIONS

Chapkin, R.S., Davidson, L.A., Park, H., Jin, U.H., Fan, Y.Y., Cheng. Y., Hensel, M.E., Landrock, K.K., Allred, C., Menon, R., Klemashevich, C., Jayaraman, A., and Safe, S. Role of the Aryl Hydrocarbon Receptor (AhR) in Mediating the Effects of Coffee in the Colon. Molecular Nutrition and Food Research. Aug 18, 2021. Online ahead of print.

Han H, Davidson LA, Hensel M, Yoon G, Landrock K, Allred C, Jayaraman A, Ivanov I, Safe SH, Chapkin RS. Loss of Aryl Hydrocarbon Receptor Promotes Colon Tumorigenesis in Apc^S580/+; Kras^G12D/+ Mice. Mol Cancer Res. 2021 May;19(5):771-783. Epub 2021 Jan 25.

Park H, Jin UH, Karki K, Allred C, Davidson LA, Chapkin RS, Orr AA, Nowshad F, Jayaraman A, Tamamis P, Safe S. Hydroxylated Chalcones as Aryl Hydrocarbon Receptor Agonists: Structure-Activity Effects. Toxicol Sci. 2021 Feb 26;180(1):148-159.

Yang F, DeLuca JAA, Menon R, Garcia-Vilarato E, Callaway E, Landrock KK, Lee K, Safe SH, Chapkin RS, Allred CD, Jayaraman A. Effect of diet and intestinal AhR expression on fecal microbiome and metabolomic profiles. Microb Cell Fact. 2020 Nov 30;19(1):219.

Park H, Jin UH, Karki K, Jayaraman A, Allred C, Michelhaugh SK, Mittal S, Chapkin RS, Safe S. Dopamine is an aryl hydrocarbon receptor agonist. Biochem J. 2020 Oct 16;477(19):3899-3910.

Han H, Davidson LA, Fan YY, Goldsby JS, Yoon G, Jin UH, Wright GA, Landrock KK, Weeks BR, Wright RC, Allred CD, Jayaraman A, Ivanov I, Roper J, Safe SH, Chapkin RS. Loss of aryl hydrocarbon receptor potentiates FoxM1 signaling to enhance self-renewal of colonic stem and progenitor cells. EMBO J. 2020 Oct 1;39(19):e104319. Epub 2020 Aug 10.

Garcia-Villatoro EL, DeLuca JAA, Callaway ES, Allred KF, Davidson LA, Hensel ME, Menon R, Ivanov I, Safe SH, Jayaraman A, Chapkin RS, Allred CD. Effects of high-fat diet and intestinal aryl hydrocarbon receptor deletion on colon carcinogenesis. Am J Physiol Gastrointest Liver Physiol. 2020 Mar 1;318(3):G451-G463. Epub 2020 Jan 6.

Park H, Jin UH, Orr AA, Echegaray SP, Davidson LA, Allred CD, Chapkin RS, Jayaraman A, Lee K, Tamamis P, Safe S. Isoflavones as Ah Receptor Agonists in Colon-Derived Cell Lines: Structure-Activity Relationships. Chem Res Toxicol. 2019 Nov 18;32(11):2353-2364. Epub 2019 Oct 29.

Villarreal D, Pradhan G, Wu CS, Allred CD, Guo S, Sun Y. A Simple High Efficiency Protocol for Pancreatic Islet Isolation from Mice. J Vis Exp. 2019 Aug 30;(150).

Yan H, Yang W, Zhou F, Li X, Pan Q, Shen Z, Han G, Newell-Fugate A, Tian Y, Majeti R, Liu W, Xu Y, Wu C, Allred K, Allred C, Sun Y, Guo S. Estrogen Improves Insulin Sensitivity and Suppresses Gluconeogenesis via the Transcription Factor Foxo1. Diabetes. 2019 Feb;68(2):291-304. Epub 2018 Nov 28.

Jin UH, Park H, Li X, Davidson LA, Allred C, Patil B, Jayaprakasha G, Orr AA, Mao L, Chapkin RS, Jayaraman A, Tamamis P, Safe S. Structure-Dependent Modulation of Aryl Hydrocarbon Receptor-Mediated Activities by Flavonoids. Toxicol Sci. 2018 Jul 1;164(1):205-217.

DeLuca JA, Allred KF, Menon R, Riordan R, Weeks BR, Jayaraman A, Allred CD. Bisphenol-A alters microbiota metabolites derived from aromatic amino acids and worsens disease activity during colitis. Exp Biol Med (Maywood). 2018 Jun;243(10):864-875. Epub 2018 Jun 6.

DeLuca JAA, Garcia-Villatoro EL, Allred CD. Flaxseed Bioactive Compounds and Colorectal Cancer Prevention. Curr Oncol Rep. 2018 Jun 5;20(8):59.

Jin UH, Cheng Y, Park H, Davidson LA, Callaway ES, Chapkin RS, Jayaraman A, Asante A, Allred C, Weaver EA, Safe S. Short Chain Fatty Acids Enhance Aryl Hydrocarbon (Ah) Responsiveness in Mouse Colonocytes and Caco-2 Human Colon Cancer Cells. Sci Rep. 2017 Aug 31;7(1):10163.

Armstrong CM, Allred KF, Weeks BR, Chapkin RS, Allred CD. Estradiol Has Differential Effects on Acute Colonic Inflammation in the Presence and Absence of Estrogen Receptor β Expression. Dig Dis Sci. 2017 Aug;62(8):1977-1984. Epub 2017 Jun 1.

Cheng Y, Jin UH, Davidson LA, Chapkin RS, Jayaraman A, Tamamis P, Orr A, Allred C, Denison MS, Soshilov A, Weaver E, Safe S. Editor’s Highlight: Microbial-Derived 1,4-Dihydroxy-2-naphthoic Acid and Related Compounds as Aryl Hydrocarbon Receptor Agonists/Antagonists: Structure-Activity Relationships and Receptor Modeling. Toxicol Sci. 2017 Feb;155(2):458-473. Epub 2016 Nov 11.

Kim E, Davidson LA, Zoh RS, Hensel ME, Salinas ML, Patil BS, Jayaprakasha GK, Callaway ES, Allred CD, Turner ND, Weeks BR, Chapkin RS. Rapidly cycling Lgr5⁺ stem cells are exquisitely sensitive to extrinsic dietary factors that modulate colon cancer risk. Cell Death Dis. 2016 Nov 10;7(11):e2460.

Kim E, Davidson LA, Zoh RS, Hensel ME, Patil BS, Jayaprakasha GK, Callaway ES, Allred CD, Turner ND, Weeks BR, Chapkin RS. Homeostatic responses of colonic LGR5+ stem cells following acute in vivo exposure to a genotoxic carcinogen. Carcinogenesis. 2016 Feb;37(2):206-14. Epub 2015 Dec 30.

Yoo G, Allred CD. The estrogenic effect of trigonelline and 3,3-diindolymethane on cell growth in non-malignant colonocytes. Food Chem Toxicol. 2016 Jan;87:23-30. Epub 2015 Nov 25.

Davidson LA, Callaway ES, Kim E, Weeks BR, Fan YY, Allred CD, Chapkin RS. Targeted Deletion of p53 in Lgr5-Expressing Intestinal Stem Cells Promotes Colon Tumorigenesis in a Preclinical Model of Colitis-Associated Cancer. Cancer Res. 2015 Dec 15;75(24):5392-7. Epub 2015 Dec 2.

Cheng Y, Jin UH, Allred CD, Jayaraman A, Chapkin RS, Safe S. Aryl Hydrocarbon Receptor Activity of Tryptophan Metabolites in Young Adult Mouse Colonocytes. Drug Metab Dispos. 2015 Oct;43(10):1536-43. Epub 2015 Apr 14.

Yang L, Allred KF, Dykes L, Allred CD, Awika JM. Enhanced action of apigenin and naringenin combination on estrogen receptor activation in non-malignant colonocytes: implications on sorghum-derived phytoestrogens. Food Funct. 2015 Mar;6(3):749-55.

Menon R, Watson SE, Thomas LN, Allred CD, Dabney A, Azcarate-Peril MA, Sturino JM. Diet complexity and estrogen receptor β status affect the composition of the murine intestinal microbiota. Appl Environ Microbiol. 2013 Sep;79(18):5763-73. Epub 2013 Jul 19.

Armstrong CM, Billimek AR, Allred KF, Sturino JM, Weeks BR, Allred CD. A novel shift in estrogen receptor expression occurs as estradiol suppresses inflammation-associated colon tumor formation. Endocr Relat Cancer. 2013 Aug;20(4):515-25.

Yang L, Allred KF, Geera B, Allred CD, Awika JM. Sorghum phenolics demonstrate estrogenic action and induce apoptosis in nonmalignant colonocytes. Nutr Cancer. 2012 Apr;64(3):419-27. Epub 2012 Feb 27.

Weige CC, Allred KF, Armstrong CM, Allred CD. P53 mediates estradiol induced activation of apoptosis and DNA repair in non-malignant colonocytes. J Steroid Biochem Mol Biol. 2012 Feb;128(3-5):113-20. Epub 2011 Nov 16.

Armstrong CM, Allred KF, Allred CD. Dietary fish oil reduces DNA adduct formation while estradiol upregulates apoptosis in response to DNA damage in the rat colon. Dig Dis Sci. 2011 Sep;56(9):2585-94. Epub 2011 Mar 16.

Weige CC, Allred KF, Allred CD. Estradiol alters cell growth in nonmalignant colonocytes and reduces the formation of preneoplastic lesions in the colon. Cancer Res. 2009 Dec 1;69(23):9118-24. Epub 2009 Nov 10.

Venditto VJ, Allred K, Allred CD, Simanek EE. Intercepting the synthesis of triazine dendrimers with nucleophilic pharmacophores: a general strategy toward drug delivery vehicles. Chem Commun (Camb). 2009 Oct 7;(37):5541-2. Epub 2009 Aug 11.

Allred KF, Yackley KM, Vanamala J, Allred CD. Trigonelline is a novel phytoestrogen in coffee beans. J Nutr. 2009 Oct;139(10):1833-8. Epub 2009 Aug 26.

Wang X, Southard RC, Allred CD, Talbert DR, Wilson ME, Kilgore MW. MAZ drives tumor-specific expression of PPAR gamma 1 in breast cancer cells. Breast Cancer Res Treat. 2008 Sep;111(1):103-11. Epub 2007 Sep 28.

Wang VC, Sable HJ, Ju YH, Allred CD, Helferich WG, Korol DL, Schantz SL. Effects of chronic estradiol treatment on delayed spatial alternation and differential reinforcement of low rates of responding. Behav Neurosci. 2008 Aug;122(4):794-804.

Talbert DR, Allred CD, Zaytseva YY, Kilgore MW. Transactivation of ERalpha by Rosiglitazone induces proliferation in breast cancer cells. Breast Cancer Res Treat. 2008 Mar;108(1):23-33.. Epub 2007 Apr 24.

Allred CD, Talbert DR, Southard RC, Wang X, Kilgore MW. PPARgamma1 as a molecular target of eicosapentaenoic acid in human colon cancer (HT-29) cells. J Nutr. 2008 Feb;138(2):250-6.

Ju YH, Allred KF, Allred CD, Helferich WG. Genistein stimulates growth of human breast cancer cells in a novel, postmenopausal animal model, with low plasma estradiol concentrations. Carcinogenesis. 2006 Jun;27(6):1292-9. Epub 2006 Mar 14.

Allred CD, Twaddle NC, Allred KF, Goeppinger TS, Churchwell MI, Ju YH, Helferich WG, Doerge DR. Soy processing affects metabolism and disposition of dietary isoflavones in ovariectomized BALB/c mice. J Agric Food Chem. 2005 Nov 2;53(22):8542-50.

Allred CD, Kilgore MW. Selective activation of PPARgamma in breast, colon, and lung cancer cell lines. Mol Cell Endocrinol. 2005 May 12;235(1-2):21-9. Epub 2005 Mar 16.

Allred CD, Allred KF, Ju YH, Goeppinger TS, Doerge DR, Helferich WG. Soy processing influences growth of estrogen-dependent breast cancer tumors. Carcinogenesis. 2004 Sep;25(9):1649-57. Epub 2004 May 6.

Allred CD, Allred KF, Ju YH, Clausen LM, Doerge DR, Schantz SL, Korol DL, Wallig MA, Helferich WG. Dietary genistein results in larger MNU-induced, estrogen-dependent mammary tumors following ovariectomy of Sprague-Dawley rats. Carcinogenesis. 2004 Feb;25(2):211-8. Epub 2003 Oct 24.

Yellayi S, Naaz A, Szewczykowski MA, Sato T, Woods JA, Chang J, Segre M, Allred CD, Helferich WG, Cooke PS. The phytoestrogen genistein induces thymic and immune changes: a human health concern?. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7616-21.

Ju YH, Doerge DR, Allred KF, Allred CD, Helferich WG. Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice. Cancer Res. 2002 May 1;62(9):2474-7.

Ju YH, Allred CD, Allred KF, Karko KL, Doerge DR, Helferich WG. Physiological concentrations of dietary genistein dose-dependently stimulate growth of estrogen-dependent human breast cancer (MCF-7) tumors implanted in athymic nude mice. J Nutr. 2001 Nov;131(11):2957-62.

Allred CD, Ju YH, Allred KF, Chang J, Helferich WG. Dietary genistin stimulates growth of estrogen-dependent breast cancer tumors similar to that observed with genistein. Carcinogenesis. 2001 Oct;22(10):1667-73.

Allred CD, Allred KF, Ju YH, Virant SM, Helferich WG. Soy diets containing varying amounts of genistein stimulate growth of estrogen-dependent (MCF-7) tumors in a dose-dependent manner. Cancer Res. 2001 Jul 1;61(13):5045-50.